Abstract 5083: Changes in HER3 expression profiles between initial diagnosis and recurrence in gynecologic cancers

Background: HER3 (ErbB-3) is a member of the epidermal growth factor receptor family of receptor tyrosine kinases, and its overexpression is associated with poorer prognosis in several cancer types. It is unclear whether HER3 expression status changes in tumor tissue at relapse. The purpose of this study is to evaluate changes in HER3 expression between initial diagnosis and recurrence in gynecologic cancers. Methods: This retrospective study included gynecologic cancer patients with matched paired tissues at the time of initial diagnosis and at the time of recurrence between 1999 and 2019 at National Cancer Center Hospital, Japan. Immunohistochemical (IHC) staining for HER3 was performed using formalin-fixed paraffin-embedded specimens. The primary antibody was HER3/ErbB3 (D22C5) XP Rabbit mAb (Cell Signaling Technology). HER3-positive was defined as an IHC score of 2+ or 3+, and HER3-negative was an IHC score of 0 or 1+, scored according to HER2 testing guidelines for gastroesophageal cancer. The H-score (range, 0-300) was calculated using the following formula: 3X+2Y+Z, where X, Y, and Z are the percentage of tumor cells showing strong, moderate, and weak staining intensity. The difference in HER3 expression between initial diagnosis and recurrence was evaluated using the χ2 test. Results: Eighty-six patients with gynecologic cancers were included (40 ovarian; 32 endometrial; 14 cervical). In ovarian cancer, 67.5% and 80.0% of the patients were HER3-positive at initial diagnosis and recurrence, respectively. There was a statistically significant increase in H-Score at recurrence (p=0.004). The HER3-positive rate in patients with endometrial cancer increased from 46.9% at initial diagnosis to 68.8% at recurrence, and H-Score tended to increase at recurrence (p=0.08). Twelve of the 14 patients (85.7%) with cervical cancer were HER3-positive, both at initial diagnosis and at recurrence, and H-Score tended to increase at recurrence (p=0.19). The discordance rate of HER3 expression determination in samples at initial diagnosis and recurrence was 27.5%, 46.9%, and 14.3% for ovarian, endometrial, and cervical cancers, respectively. Conclusion: Our findings suggest that HER3 expression may increase at recurrence in patients with gynecologic cancers. HER3-targeted therapy may represent a promising option to overcome treatment failure and improve patient outcomes. Citation Format: Yuki Kojima, Kazuki Sudo, Hiroshi Yoshida, Shu Yazaki, Momoko Tokura, Shosuke Kita, Kasumi Yamamoto, Chiharu Mizoguchi, Hitomi S Okuma, Tadaaki Nishikawa, Emi Noguchi, Tatsunori Shimoi, Yasuhito Tanase, Masaya Uno, Mitsuya Ishikawa, Tomoyasu Kato, Kumiko Koyama, Maki Kobayashi, Tomoya Kakegawa, Yasuhiro Fujiwara, Kan Yonemori. Changes in HER3 expression profiles between initial diagnosis and recurrence in gynecologic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5083.